What is the management for Hypertrophic Obstructive Cardiomyopathy (HOCM)?

Management of Hypertrophic Obstructive Cardiomyopathy (HOCM)

Beta-blockers are the first-line pharmacologic therapy for symptomatic HOCM, titrated to achieve a resting heart rate of 60-65 bpm, with non-dihydropyridine calcium channel blockers (verapamil or diltiazem) as second-line agents when beta-blockers fail or are contraindicated. 1

Initial Pharmacologic Management Algorithm

First-Line Therapy

• Beta-blockers are the primary initial treatment for both obstructive and nonobstructive symptomatic HCM, targeting a resting heart rate <60-65 bpm 1
• Beta-blockers reduce LVOT gradients, alleviate dyspnea, and improve quality of life in 30-70% of patients 2, 3
• Common side effects include bradycardia, hypotension, and risk of AV nodal blockade 2

Second-Line Therapy

• Verapamil or diltiazem (non-dihydropyridine calcium channel blockers only) should be used when beta-blockers are ineffective, not tolerated, or contraindicated 1
• Verapamil can be titrated up to 480 mg/day for symptom control 1
• Verapamil improves physical resilience and provides favorable results in medically managed patients 2, 3
• Critical warning: Verapamil should be avoided in patients with severe left ventricular dysfunction (ejection fraction <30%) or moderate to severe heart failure symptoms 4
• In patients with HOCM, verapamil-related pulmonary edema and severe hypotension have occurred, particularly in those with severe LVOT obstruction and past history of left ventricular dysfunction 4

Advanced Medical Therapy

Mavacamten (Cardiac Myosin Inhibitor)

• Mavacamten is recommended (Class 1) for adults with persistent NYHA class II-III symptoms despite beta-blockers or calcium channel blockers 1, 5
• Mavacamten improves LVOT gradients, functional capacity, and quality of life in 30-60% of patients with obstructive HCM 5
• Mandatory REMS program monitoring required: LVEF reduction <50% occurs in 5.7% attributable to the drug alone, up to 7-10% when considering other clinical conditions 5
• Must discontinue if persistent systolic dysfunction (LVEF <50%) develops 5
• Contraindicated in pregnancy due to teratogenic effects 5
• Regular echocardiographic monitoring is essential 5

Disopyramide

• Disopyramide is an alternative third-line agent when beta-blockers and calcium channel blockers fail 6
• Should not be administered within 48 hours before or 24 hours after verapamil due to potential interactions 4

Adjunctive Therapy

• Diuretics: Use cautiously at low doses for congestive symptoms, as aggressive diuresis can worsen LVOT obstruction by decreasing preload 6
• Diuretics and vasodilators should be avoided in symptomatic patients with LVOT obstruction, though they can be used in asymptomatic patients 6

Septal Reduction Therapy (SRT)

Indications for SRT

• SRT is recommended (Class 1) for patients with obstructive HCM who remain symptomatic despite guideline-directed medical therapy (GDMT) 6
• Eligibility criteria include:
  • Severe dyspnea or chest pain (usually NYHA class III or IV) attributable to LVOTO that interferes with everyday activity despite optimal medical therapy 6
  • Dynamic LVOT gradient at rest or with physiologic provocation with peak gradient ≥50 mmHg 6

Surgical Myectomy

• Surgical myectomy is the preferred SRT when performed by experienced operators at comprehensive HCM centers, achieving >90% relief of obstruction with perioperative mortality <1% in most centers 6, 7, 8
• Mandatory for patients requiring concomitant cardiac surgery (anomalous papillary muscle, elongated anterior mitral leaflet, intrinsic mitral valve disease, multivessel CAD, valvular aortic stenosis) 6
• Long-term outcomes show cumulative survival of 88% at 10 years and 72% at 20-26 years, with disease-related mortality reduced to 0.6% per year 8
• Earlier myectomy (NYHA class II) may be reasonable in presence of:
  • Severe progressive pulmonary hypertension attributable to LVOTO or associated MR 6
  • Left atrial enlargement with ≥1 episodes of symptomatic atrial fibrillation 6
  • Poor functional capacity attributable to LVOTO on treadmill testing 6
  • Children and young adults with very high resting LVOT gradients (>100 mmHg) 6

Alcohol Septal Ablation

• Recommended (Class 1) for adult patients who remain severely symptomatic despite GDMT when surgery is contraindicated or risk is unacceptable due to serious comorbidities or advanced age 6
• Less invasive alternative with hemodynamic and clinical results comparable to myectomy in many patients 7, 9
• Results are dependent on septal perforator artery anatomy; younger patients with severe hypertrophy may not experience complete relief 7
• Creates controlled septal infarction resulting in relief of symptoms, decreased pressure gradient, and improved LV diastolic function 9

SRT as Alternative to Medical Escalation

• SRT may be considered as an alternative to escalation of medical therapy after shared decision-making including risks and benefits of all treatment options (Class 2b) 6
• SRT is not recommended for asymptomatic patients with normal exercise capacity 6

Critical Medications to AVOID in HOCM

Absolutely Contraindicated

• Dihydropyridine calcium channel blockers (amlodipine, nifedipine, felodipine) are potentially harmful (Class III: Harm) in patients with resting or provocable LVOT obstruction 1
• Alpha-blockers (terazosin, doxazosin) cause vasodilation that can worsen LVOT obstruction and precipitate hemodynamic collapse 1
• Nitrates and hydralazine should be avoided in obstructive HCM 1

Use with Extreme Caution

• ACE inhibitors and ARBs have uncertain benefit and are potentially harmful in patients with resting or provocable LVOT obstruction 1
• Inotropes (dopamine, dobutamine) should never be used in acute hypotension with obstructive HCM 1

Management of Acute Hypotension in HOCM

• Acute hypotension in obstructive HCM is a medical urgency requiring immediate intervention 6
• Treatment priorities: Maximize preload and afterload while avoiding increases in contractility or heart rate 6
• Phenylephrine (pure vasoconstrictor) is the preferred agent to reverse acute hypotension 6, 1
• Beta-blockade can be useful in combination with vasoconstrictors to dampen contractility and improve preload by prolonging diastolic filling 6
• In patients with HOCM experiencing hypotension, alpha-adrenergic agents (phenylephrine, metaraminol, or methoxamine) should be used to maintain blood pressure; isoproterenol and norepinephrine should be avoided 4

Management of Comorbidities

Hypertension

• Beta-blockers and non-dihydropyridine calcium channel blockers are preferred antihypertensive agents in obstructive HCM 6, 1
• Lifestyle modifications and medical therapy for hypertension are recommended (Class 1) 6

Obesity

• Counseling and comprehensive lifestyle interventions are recommended (Class 1) for achieving and maintaining weight loss, potentially lowering risk of developing LVOTO, heart failure, and atrial fibrillation 6
• Obesity is present in >70% of adult HCM patients and is independently associated with increased burden of LVH, more symptoms, and worse outcomes 6

Sleep-Disordered Breathing

• Assessment for symptoms of sleep-disordered breathing is recommended (Class 1), with referral to sleep medicine specialist if present 6
• Sleep-disordered breathing affects 55-70% of HCM patients and is associated with greater symptom burden, reduced exercise capacity, and higher prevalence of atrial fibrillation and NSVT 6

Treatment Hierarchy Summary

The current evidence-based treatment algorithm is:

1. Beta-blockers (first-line)
2. Verapamil or diltiazem (second-line)
3. Mavacamten, disopyramide, or septal reduction therapy (third-line for persistent symptoms) 5